Potential of PSMA-targeting radioligand therapy for malignant primary and secondary brain tumours using super-selective intra-arterial administration: a single centre, open label, non-randomised prospective imaging study.

BACKGROUND: The aim of this study was to provide quantitative evidence for the potential of PSMA-targeting radioligand therapy (RLT) as treatment approach for malignant brain tumours, and to explore whether tumour uptake could be enhanced by super-selective intra-arterial (ssIA)-administration. METHODS: Ten patients (n = 5 high-grade glioma, n = 5 brain metastasis) received 1.5 MBq/kg [68Ga]Ga-PSMA-11 intravenously and, within 7 days, intra-arterially (i.e., selectively in tumour-feeding arteries), followed twice by PET-MRI at 90, 165 and 240 min post-injection. Patient safety was monitored for each procedure. Standardised uptake values (SUVs) were obtained for tumour, healthy-brain, salivary glands and liver. Tumour-to-salivary-gland (T/SG) and tumour-to-liver (T/L) uptake-ratios were calculated. FINDINGS: No adverse events requiring study termination occurred. All patients showed uptake of [68Ga]Ga-PSMA-11 at the tumour site. Uptake was a median 15-fold higher following ssIA-administration (SUVmax median: 142.8, IQR: 102.8-245.9) compared to IV-administration (10.5, IQR:7.5-13.0). According to the bootstrap analysis, mean SUVmax after ssIA (168.8, 95% CI: 110.6-227.0) was well beyond the 95% confidence-interval of IV administration (10.5, 95% CI: 8.4-12.7). Uptake in healthy-brain was negligible, independent of administration route (SUVmean <0.1-0.1). Off-target uptake was comparable, resulting in more favourable T/SG- and T/L-ratios of 8.4 (IQR: 4.4-11.5) and 26.5 (IQR: 14.0-46.4) following ssIA, versus 0.5 (IQR: 0.4-0.7) and 1.8 (IQR: 1.0-2.7) for IV-administration. INTERPRETATION: ssIA-administration is safe and leads to a median fifteen-fold higher radioligand uptake at the tumour site, therewith qualifying more patients for treatment and enhancing the potential of therapy. These results open new avenues for the development of effective RLT-based treatment strategies for patients with brain tumours. FUNDING: Semmy Foundation.

Influence of the interventionist's experience on outcomes of endovascular thrombectomy in acute ischemic stroke: results from the MR CLEAN Registry.

BACKGROUND: The relationship between the interventionist's experience and outcomes of endovascular thrombectomy (EVT) for acute ischemic stroke of the anterior circulation, is unclear. OBJECTIVE: To assess the effect of the interventionist's level of experience on clinical, imaging, and workflow outcomes. Secondly, to determine which of the three experience definitions is most strongly associated with these outcome measures. METHODS: We analysed data from 2700 patients, included in the MR CLEAN Registry. We defined interventionist's experience as the number of procedures performed in the year preceding the intervention (EXPfreq), total number of procedures performed (EXPno), and years of experience (EXPyears). Our outcomes were the baseline-adjusted National Institutes of Health Stroke Scale (NIHSS) score at 24-48 hours post-EVT, recanalization (extended Thrombolysis in Cerebral Infarction (eTICI) score ≥2B), and procedural duration. We used multilevel regression models with interventionists as random intercept. For EXPfreq and EXPno results were expressed per 10 procedures. RESULTS: Increased EXPfreq was associated with lower 24-48 hour NIHSS scores (adjusted (a)ß:-0.46, 95% CI -0.70 to -0.21). EXPno and EXPyears were not associated with short-term neurological outcomes. Increased EXPfreq and EXPno were both associated with recanalization (aOR=1.20, 95% CI 1.11 to 1.31 and aOR=1.08, 95% CI 1.04 to 1.12, respectively), and increased EXPfreq, EXPno, and EXPyears were all associated with shorter procedure times (aß:-3.08, 95% CI-4.32 to -1.84; aß:-1.34, 95% CI-1.84 to -0.85; and aß:-0.79, 95% CI-1.45 to -0.13, respectively). CONCLUSIONS: Higher levels of interventionist's experience are associated with better outcomes after EVT, in particular when experience is defined as the number of patients treated in the preceding year. Every 20 procedures more per year is associated with approximately one NIHSS score point decrease, an increased probability for recanalization (aOR=1.44), and a 6-minute shorter procedure time.

Effect of first pass reperfusion on outcome in patients with posterior circulation ischemic stroke.

BACKGROUND: First pass reperfusion (FPR), that is, excellent reperfusion (expanded treatment in cerebral ischemia (eTICI) 2C-3) in one pass, after endovascular treatment (EVT) of an occluded artery in the anterior circulation, is associated with favorable clinical outcome, even when compared with multiple pass excellent reperfusion (MPR). In patients with posterior circulation ischemic stroke (PCS), the same association is expected, but currently unknown. We aimed to assess characteristics associated with FPR and the influence of FPR versus MPR on outcomes in patients with PCS. METHODS: We used data from the MR CLEAN Registry, a prospective observational study. The effect of FPR on 24-hour National Institutes of Health Stroke Scale (NIHSS) score, as percentage reduction, and on modified Rankin Scale (mRS) scores at 3 months, was tested with linear and ordinal logistic regression models. RESULTS: Of 224 patients with PCS, 45 patients had FPR, 47 had MPR, and 90 had no excellent reperfusion (eTICI <2C). We did not find an association between any of the patient, imaging, or treatment characteristics and FPR. FPR was associated with better NIHSS (-45% (95% CI: -65% to -12%)) and better mRS scores (adjusted common odds ratio (acOR): 2.16 (95% CI: 1.23 to 3.79)) compared with no FPR. Outcomes after FPR were also more favorable compared with MPR, but the effect was smaller and not statistically significant (NIHSS: -14% (95% CI: -51% to 49%), mRS acOR: 1.50 (95% CI: 0.75 to 3.00)). CONCLUSIONS: FPR in patients with PCS is associated with favorable clinical outcome in comparison with no FPR. In comparison with MPR, the effect of FPR was no longer statistically significant. Nevertheless, our data support the notion that FPR should be the treatment target to pursue in every patient treated with EVT.

Diagnostic performance of an algorithm for automated large vessel occlusion detection on CT angiography.

BACKGROUND: Machine learning algorithms hold the potential to contribute to fast and accurate detection of large vessel occlusion (LVO) in patients with suspected acute ischemic stroke. We assessed the diagnostic performance of an automated LVO detection algorithm on CT angiography (CTA). METHODS: Data from the MR CLEAN Registry and PRESTO were used including patients with and without LVO. CTA data were analyzed by the algorithm for detection and localization of LVO (intracranial internal carotid artery (ICA)/ICA terminus (ICA-T), M1, or M2). Assessments done by expert neuroradiologists were used as reference. Diagnostic performance was assessed for detection of LVO and per occlusion location by means of sensitivity, specificity, and area under the curve (AUC). RESULTS: We analyzed CTAs of 1110 patients from the MR CLEAN Registry (median age (IQR) 71 years (60-80); 584 men; 1110 with LVO) and of 646 patients from PRESTO (median age (IQR) 73 years (62-82); 358 men; 141 with and 505 without LVO). For detection of LVO, the algorithm yielded a sensitivity of 89% in the MR CLEAN Registry and a sensitivity of 72%, specificity of 78%, and AUC of 0.75 in PRESTO. Sensitivity per occlusion location was 88% for ICA/ICA-T, 94% for M1, and 72% for M2 occlusion in the MR CLEAN Registry, and 80% for ICA/ICA-T, 95% for M1, and 49% for M2 occlusion in PRESTO. CONCLUSION: The algorithm provided a high detection rate for proximal LVO, but performance varied significantly by occlusion location. Detection of M2 occlusion needs further improvement.

Predictors of poor outcome despite successful endovascular treatment for ischemic stroke: results from the MR CLEAN Registry.

BACKGROUND: Approximately one-third of patients with ischemic stroke treated with endovascular treatment do not recover to functional independence despite rapid and successful recanalization. We aimed to quantify the importance of predictors of poor functional outcome despite successful reperfusion. METHODS: We analyzed patients from the MR CLEAN Registry between March 2014 and November 2017 with successful reperfusion (extended Thrombolysis In Cerebral Infarction ≥2B). First, predictors were selected based on expert opinion and were clustered according to acquisition over time (ie, baseline patient factors, imaging factors, treatment factors, and postprocedural factors). Second, several models were constructed to predict 90-day functional outcome (modified Rankin Scale (mRS)). The relative importance of individual predictors in the most extensive model was expressed by the proportion of unique added χ2 to the model of that individual predictor. RESULTS: Of 3180 patients, 1913 (60%) had successful reperfusion. Of these 1913 patients, 1046 (55%) were functionally dependent at 90 days (mRS >2). The most important predictors for mRS were baseline patient factors (ie, pre-stroke mRS, added χ2 0.16; National Institutes of Health Stroke Scale score at baseline, added χ2 0.12; age, added χ2 0.10), and postprocedural factors (ie, symptomatic intracranial hemorrhage (sICH), added χ2 0.12; pneumonia, added χ2 0.09). The probability of functional independence for a typical stroke patient with sICH was 54% (95% CI 36% to 72%) lower compared with no sICH, and 21% (95% CI 4% to 38%) for pneumonia compared with no pneumonia. CONCLUSION: Baseline patient factors and postprocedural adverse events are important predictors of poor functional outcome in successfully reperfused patients with ischemic stroke. This implies that prevention of postprocedural adverse events has the greatest potential to further improve outcomes in these patients.

The Efficacy of Coil Embolization to Obtain Intrahepatic Redistribution in Radioembolization: Qualitative and Quantitative Analyses.

PURPOSE: To evaluate the efficacy of coil embolization to obtain intrahepatic redistribution in patients undergoing radioembolization. MATERIALS AND METHOD: All patients treated with radioembolization at our institute were retrospectively analyzed, and all cases in which a tumor-feeding vessel was coil-embolized were selected. Two nuclear medicine physicians visually assessed the effect of redistribution. Furthermore, the redistribution of microspheres was measured by quantifying the activity distributed to the coil-embolized (dependent) segment relative to the other (non-dependent) segments and to the tumor(s) in that segment. Quantitative analysis was performed on post-treatment 90Y-PET and 166Ho-SPECT using Simplicit90Y software. Lesion response was measured according to RECIST 1.1 criteria at 3 months post-treatment. RESULTS: Out of 37 cases, 32 were suitable for quantitative analysis and 37 for qualitative analysis. In the qualitative analysis, redistribution was deemed successful in 69% of cases. The quantitative analysis showed that the median ratio of the activity to the dependent embolized segments and the non-dependent segments was 0.88 (range 0.26-2.05) and 0.80 (range 0.19-1.62) for tumors in dependent segments compared with tumors in non-dependent segments. Using a cutoff ratio of 0.7 (30% lower activity concentration in comparison with the rest of the liver), 57% of cases were successful. At 3 months post-treatment, 6% of dependent tumors had partial response, 20% progressive disease, and 74% stable disease. In non-dependent tumors, this was, respectively, 16%, 20%, and 64%. CONCLUSION: Coil embolization of hepatic arteries to induce redistribution of microspheres has a limited success rate. Qualitative assessment tends to overrate redistribution.

Distal Radial Artery Access for Noncoronary Endovascular Treatment Is a Safe and Feasible Technique.

PURPOSE: To evaluate safety and feasibility of distal radial artery (DRA) access for noncoronary interventional radiology procedures. MATERIALS AND METHODS: All interventional radiology procedures by means of DRA puncture from July 2017 to August 2018 were retrospectively reviewed. Eighty-two punctures in 56 patients were included, mostly in male patients (84% vs 16%). Mean age was 67.8 years (range, 33.3-87.3 years); mean height was 172 cm (range, 142-190 cm); and mean weight was 83 kg (range, 43-120 kg). Procedural characteristics, technical success, and complication rates were gathered from the medical records and follow-up ultrasound when available. Prerequisites for DRA access were adequate radioulnar collateral circulation, sufficient radial artery diameter, and informed consent in patients initially intended for conventional transradial access. RESULTS: Procedures included transarterial chemoembolization (n = 34), yittrium-90 pretreatment angiography (n = 21), yittrium-90 administration (transarterial radioembolization; n = 20), and embolization of visceral organs (n = 7). Both 4-Fr (n = 35) and 5-Fr (n = 46) sheaths were used. Technical success of DRA access was 97.6%, with conversion to transfemoral access in 2 cases (2.4%). No major complications were reported as a result of DRA access. CONCLUSION: DRA access is a feasible and safe technique for abdominal interventional radiology embolization procedures. No radial artery occlusion or other major complications were observed in patients who underwent follow-up ultrasound.